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排序方式: 共有1377条查询结果,搜索用时 31 毫秒
161.
Søren Bak Susanne Michelle Paquette Marc Morant Anne Vinther Morant Shigeki Saito Nanna Bjarnholt Mika Zagrobelny Kirsten Jørgensen Sarah Osmani Henrik Toft Simonsen Raquel Sanchez Pérez Torbjørn Bordier van Heeswijck Bodil Jørgensen Birger Lindberg Møller 《Phytochemistry Reviews》2006,5(2-3):309-329
Cyanogenic glycosides are ancient biomolecules found in more than 2,650 higher plant species as well as in a few arthropod species. Cyanogenic glycosides are amino acid-derived β-glycosides of α-hydroxynitriles. In analogy to cyanogenic plants, cyanogenic arthropods may use cyanogenic glycosides as defence compounds. Many of these arthropod species have been shown to de novo synthesize cyanogenic glycosides by biochemical pathways that involve identical intermediates to those known from plants, while the ability to sequester cyanogenic glycosides appears to be restricted to Lepidopteran species. In plants, two atypical multifunctional cytochromes P450 and a soluble family 1 glycosyltransferase form a metabolon to facilitate channelling of the otherwise toxic and reactive intermediates to the end product in the pathway, the cyanogenic glycoside. The glucosinolate pathway present in Brassicales and the pathway for cyanoalk(en)yl glucoside synthesis such as rhodiocyanosides A and D in Lotus japonicus exemplify how cytochromes P450 in the course of evolution may be recruited for novel pathways. The use of metabolic engineering using cytochromes P450 involved in biosynthesis of cyanogenic glycosides allows for the generation of acyanogenic cassava plants or cyanogenic Arabidopsis thaliana plants as well as L. japonicus and A. thaliana plants with altered cyanogenic, cyanoalkenyl or glucosinolate profiles. 相似文献
162.
Masanori Noguchi Tatsuyuki Kakuma Hirotsugu Uemura Yasutomo Nasu Hiromi Kumon Yasuhiko Hirao Fukuko Moriya Shigetaka Suekane Kei Matsuoka Nobukazu Komatsu Shigeki Shichijo Akira Yamada Kyogo Itoh 《Cancer immunology, immunotherapy : CII》2010,59(7):1001-1009
Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14–0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1–0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone. 相似文献
163.
Masafumi Minoshima Toshikazu Bando Ken-ichi Shinohara Gengo Kashiwazaki Shigeki Nishijima Hiroshi Sugiyama 《Bioorganic & medicinal chemistry》2010,18(3):1236-1243
We investigated sequence-specific DNA alkylation using conjugates between the N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide and the DNA alkylating agent, chlorambucil, or 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). Polyamide–chlorambucil conjugates 1–4 differed in the position at which the DNA alkylating chlorambucil moiety was bound to the Py–Im polyamide. High-resolution denaturing polyacrylamide gel electrophoresis (PAGE) revealed that chlorambucil conjugates 1–4 alkylated DNA at the sequences recognized by the Py–Im polyamide core moiety. Reactivity and sequence specificity were greatly affected by the conjugation position, which reflects the geometry of the alkylating agent in the DNA minor groove. Polyamide–seco-CBI conjugate 5 was synthesized to compare the efficacy of chlorambucil with that of seco-CBI as an alkylating moiety for Py–Im polyamides. Denaturing PAGE analysis revealed that DNA alkylation activity of polyamide–seco-CBI conjugate 5 was similar to that of polyamide–chlorambucil conjugates 1 and 2. In contrast, the cytotoxicity of conjugate 5 was superior to that of conjugates 1–4. These results suggest that the seco-CBI conjugate was distinctly active in cells compared to the chlorambucil conjugates. These results may contribute to the development of more specific and active DNA alkylating agents. 相似文献
164.
Zhichun Li Osamu Nakagawa Yohei Koga Yosuke Taniguchi Shigeki Sasaki 《Bioorganic & medicinal chemistry》2010,18(11):3992-3998
8-Oxoguanosine (8-oxoG) is a representative metabolite derived by the oxidation of guanosine (G) and is regarded as a marker of oxidative stress in the cells. We previously reported the 8-oxoG-clamp as the first fluorescent probe for detection of 8-oxoG. In this study, new 8-oxoG-clamp derivatives having a variety of N-functional groups were synthesized and their recognition properties were investigated. The sp3 oxygen atom of the carbamate unit was revealed to play a significant role in the hydrogen bonding interactions, and the pyrene group produced higher stability with 8-oxoG compared with the original 8-oxoG-clamp. 相似文献
165.
166.
Saito S Okamoto M Shinoda S Kushiro T Koshiba T Kamiya Y Hirai N Todoroki Y Sakata K Nambara E Mizutani M 《Bioscience, biotechnology, and biochemistry》2006,70(7):1731-1739
Plant growth retardants (PGRs) reduce the shoot growth of plants by inhibiting gibberellin biosynthesis. In this study, we performed detailed analyses of the inhibitory effects of PGRs on Arabidopsis abscisic acid (ABA) 8'-hydroxylase, a major ABA catabolic enzyme, recently identified as CYP707As. In an in vitro assay with CYP707A3 microsomes expressed in insect cells, uniconazole-P inhibited CYP707A3 activity more effectively than paclobutrazol or tetcyclacis, whereas the other PGRs tested did not inhibit it significantly. Uniconazole-P was found to be a strong competitive inhibitor (K(i)=8.0 nM) of ABA 8'-hydroxylase. Uniconazole-P-treated Arabidopsis plants showed enhanced drought tolerance. In uniconazole-P-treated plants, endogenous ABA levels increased 2-fold as compared with the control, and co-application of GA(4) did not suppress the effects, indicating that the effects were not due to gibberellin deficiency. Thus uniconazole-P effectively inhibits ABA catabolism in Arabidopsis plants. We also discuss the structure-activity relationship of the azole-type compounds on ABA 8'-hydroxylase inhibitory activity. 相似文献
167.
Ikuzawa M Shimizu K Yasumasu S Iuchi I Shi YB Ishizuya-Oka A 《Development genes and evolution》2006,216(3):109-118
168.
169.
Chemical entities that specifically interact with biological molecules can reveal the biological role of their targets. Increasing knowledge of genomes and the intricate mechanisms that regulate their expression has aroused considerable interest in molecules that target nucleic acids. A wide variety of technologies have been developed based on unnatural oligonucleotides for gene silencing, gene-detection or bio-inspired chemical reactions, for example. In contrast to natural oligonucleotides, their unnatural counterparts can exhibit unique functions based on the chemical reactivity of the accessory molecule. This review focuses on the molecular design of chemically reactive accessory molecules of unnatural oligonucleotides, emphasising their application in specific recognition and reaction toward biological targets. 相似文献
170.